The National NeuroAIDS Tissue Consortium (NNTC) is a national repository for CNS and PNS specimens that opened the way for fundamental research on the mechanism and treatment of HIV-related neurocognitive disease. The early phase of the project focused on forming the National Steering Committee to standardize the protocol Subjects were recruited, neurocognitive impairment was assessed, structured neurological examinations were performed, substance use was documented, and blood and CSF virologic status were determined. A quality assurance (QA) program was implemented to control for variability between sites, and a web-based database was established. A National Coordinating Office was established to process specimen requests, and to provide data to the community (www.hivbrainbanks.org). After 3 3/4 years, the NNTC recruited a cohort that produced about 165 well-characterized HIV-infected decedents who underwent autopsy. There are over 600 active subjects in the cohort likely to undergo autopsy in the future. Investigators can use these data to compare new discoveries with the clinical information that we have collected. The Texas HIV Brain Bank operates a website that offers vetted investigators additional options. Our repository responded effectively to over 91 % of all NNTC specimen requests. Much more neurochemical, molecular and morphological study of human CNS specimens needs to be performed on these resources. To continue building durable assets and serving the research community, we propose to continue operating the Texas Repository in a renewed NNTC project. We will follow to autopsy, over the next five years, 129 well-characterized HIV infected subjects in the Texas NNTC cohort. We will carry out a brain bank resource utilization program to address the scientific themes of our site. We will: 1) perform gene expression profiles on dorsal root ganglia from patients with peripheral neuropathy (DSP); 2) determine if a polymorphic TNF-a allele is over-represented in people with DSP and/or dementia; 3) isolate microglial cells from human autopsy brain, infect them with HIV-1, and distribute cells and media to the research community; 4) construct a linear multiple regression model of brain cell counts, including subspecies of mononuclear phagocytes, brain HIV loads, and neurochemical changes to determine their clinical relevancy in our cohort.